The Myelin Project

Making rare diseases a public-health and research priority

noemail@myelin.org — Tue, 17 Jun 2008 16:00:00 GMT

Editorial 1972 www.thelancet.com Vol 371 June 14, 2008 Making rare diseases a public-health and research priority On May 30, a 30-year-old man with adrenoleukodystrophy died of pneumonia. Lorenzo Odone was a remarkable individual from a remarkable family. He lived for 24 years after his adrenoleukodystrophy was diagnosed (20 years longer than predicted). His longevity might have been, in part, due to the combination of erucic and oleic acids that were added to his diet by his parents. Michaela (who had been a publishing editor until her son was born) and Augusto (an economist) refused to accept there was no treatment for their son. By trawling through published hypotheses and research, they con cluded that a 4:1 mixture of glyceryl trioleate and glyceryl trierucate lowers the plasma concentrations of saturated very-longchain fatty acids, which are involved in the demyelination in adrenoleukodystrophy. Lorenzo’s oil, as it became known, was tested in trials led by Lorenzo’s...

Rare Diseases Whats next?

noemail@myelin.org — Tue, 17 Jun 2008 16:00:00 GMT

Rare diseases: what’s next? Rare diseases are life-threatening or chronically debilitating diseases with a prevalence lower than one per 2000 in the European Community or one per 1250 in the USA. Only a few of the 5000 recognised rare diseases have a prevalence close to those limits, and most of them are much rarer, such as muscular dystrophy, or haemophilia, and others are so uncommon that they are defi ned as being ultra-rare, such as Hutchinson-Gilford syndrome (progeria), or Whipple’s disease. Rare diseases are also called health orphans—for most of them there is little knowledge of causes and eff ective therapies are limited. However, rare diseases are now included as priorities in public-health plans, and research-funding programmes in Europe and the USA are increasingly promoting basic and clinical research on these disorders. The five essays in today’s Lancet look at current activity in research into and treatment of rare diseases.(1-5) As an example, in response to...

Zymenex gets FDA approval of Investigational New Drug

noemail@myelin.org — Mon, 16 Jun 2008 18:00:00 GMT

Press release Hillerød, Denmark , March 10 , 2008 Zymenex gets FDA approval of IND Zymenex has received FDA approval of its Investigational New Drug (IND) application for its enzyme Metazym, which is intended for use in the treatment of the rare, lysosomal disease Metachromatic Leukodystrophy (MLD). The company is now preparing for Phase 2 clinical trials in the USA. This milestone is very important and paves the way towards a treatment for the patients in the USA suffering from this lethal disease, says CEO Jens Fogh, Zymenex A/S. The Phase 2 trial will include 10 patients with late-infantile MLD and will be performed by Dr. Maria L. Escolar at the Program for Neurodevelopmental Function in Rare Disorders, Center for the Study of Development and Learning, University of North Carolina (UNC), Chapel Hill, North Carolina, USA. The FDA IND approval is the first step towards being able to initiate the trial. The trial protocol must now be approved by the Ethical...

Metachromatic Leukodystrophy Clinical Trial

noemail@myelin.org — Mon, 02 Jun 2008 03:00:00 GMT

To those with new diagnosis of Metachromatic Leukodystrophy:

Your child may be able to participate in the upcoming Metazym Clinical Trial to be conducted at the University of North Carolina (UNC). Screening for 10-12 children is now in progress. Please contact Dr. Maria Escolar at (919)966-4810 for more information.

LORENZO ODONE PASSED AWAY MAY 30, 2008

noemail@myelin.org — Sat, 31 May 2008 02:00:00 GMT

Press Release
5/30/2008

Lorenzo Odone, whose story was told in the 1992 Hollywood movie "Lorenzo's Oil", starring Susan Sarandon and Nick Nolte, has died in Fairfax, VA, one day after his 30th birthday. Lorenzo was diagnosed with Adrenoleukodystrophy (ALD) in 1984, aged 6. Doctors told his parents that the neurological disease would swiftly deprive him of all his faculties and lead to his death withing a maximum of two years.

Odone's parents, Augusto and Michaela, despite having no scientific background, decided to research the rare genetic disorder. Their struggle and ultimate triumph, when they found an oil that stopped the disease in its tracks and, in pre-symptomatic boys, prevented the onslaught of ALD, captivated director George Miller, who went on to make 'Happy Feet' and 'The Witches of Eastwick'. He turned the true life story into a film which won Susan Sarandon an Oscar nomination as Best Actress.

(Sarandon insisted on bringing Michaela Odone with her to the Oscar

ceremonies.)

The film met with criticism from the medical community, who condemned it for setting up false hopes in families of ALD sufferers. The Odones however were amply vindicated by a study published two years ago, which showed that Lorenzo's Oil did indeed stop ALD in pre-symptomatic boys.

The Odones also founded the Myelin Project, a mould-breaking medical research charity which as well as providing leadership in the search for a cure for ALD< also enabled families affected by the disease to meet directly with scientists working in the field "Scientists should never forget that their mission is to relieve human suffering rather than win the Nobel prize" said Augusto Odone when founding the project.

In 1996, Phil Collins wrote the song "Lorenzo", based on lyrics written by Michaela.

Bedridden and unable to communicate from his seventh year, Lorenzo was kept at home by his parents. Nurses cared for him round the clock, as did his indefatigable parents. Lorenzo outlived his mother, who died of lung cancer in 2002. He is survived by his father, Augusto, his brother Francesco and sister and Cristina.

New Class of Drugs for Treatment of Multiple Sclerosis

noemail@myelin.org — Wed, 21 May 2008 14:00:00 GMT

Prog Drug Res. 2008;66:361, 363-81.Links
Ascomycete derivative to MS therapeutic: S1P receptor modulator FTY720.

Hiestand PC, Rausch M, Meier DP, Foster CA.

Novartis Pharma AG, Lichtstrasse 35, 4002 Basel, Switzerland.

Fingolimod (FTY720) represents the first in a new class of immune-modulators whose target is sphingosine-1-phosphate (S1P) receptors.

It was first identified by researchers at Kyoto University and Yoshitomi Pharmaceutical as a chemical derivative of the ascomycete metabolite ISP-1 (myriocin). Unlike its natural product parent, FTY720 does not interfere with sphingolipid biosynthesis. Instead, its best characterized mechanism of action upon in vivo phosphorylation, leading to the active principle FTY720-P, is the rapid and reversible inhibition of lymphocyte egress from peripheral lymph nodes. As a consequence of S1P1 receptor internalization, tissue-damaging T-cells can not recirculate and infiltrate sites of inflammation such as the central nervous system (CNS). Furthermore, FTY720-P modulation of S1P receptor signaling also enhances endothelial barrier function. Due to its mode of action, FTY720 effectively prevents transplant rejection and is active in various autoimmune disease models. The most striking efficacy is in the multiple sclerosis (MS) model of experimental autoimmune encephalomyelitis, which has now been confirmed in the clinic.

FTY720 demonstrated promising results in Phase II trials and recently entered Phase III in patients with relapsing MS. Emerging evidence suggests that its efficacy in the CNS extends beyond immunomodulation to encompass other aspects of MS pathophysiology, including an influence on the blood-brain-barrier and glial repair mechanisms that could ultimately contribute to restoration of nerve function. FTY720 may represent a potent new therapeutic modality in MS, combined with the benefit of oral administration.

Carolyn A. Foster, Ph.D.
Senior Research Investigator
Novartis Institutes for BioMedical Research
Brunner Strasse 59
A-1235 Vienna, Austria

office tel: +43 1 86634-685
mobile: +43 664 80166-6850
email: carolyn.foster@novartis.com

StopALD Foundation Funds Gene Therapy

noemail@myelin.org — Mon, 19 May 2008 15:00:00 GMT

The research and clinical trial discussed in the article below was sponsored in part by The Stop ALD Foundation. To see all recent Stop ALD Foundation news please click here. Published online 30 October 2007 | Nature | doi:10.1038/news.2007.204 Gene therapy sees early success for neurodegenerative disease Treatment uses HIV to insert genetic material into ALD patients. Declan Butler Two children with a common neurodegenerative disease are seeing early signs of success from a pioneering gene-therapy treatment, researchers report this week. The results raise hopes for a treatment for adrenoleukodystrophy (ALD), and, the researchers add, mark the first successful use of an attenuated HIV virus to carry a therapeutic gene into a patient’s cells. HIV is a promising vector for transferring corrective genes into a host — it can penetrate directly into cell nuclei, making it a theoretically efficient way to introduce new genetic material. But until now it hadn’t been proven in...

NORTHWOOD SCHOOL STUDENTS RAISE MONEY FOR MYELIN DISEASE RESEARCH

noemail@myelin.org — Mon, 12 May 2008 21:00:00 GMT

NEWS 10 NOW NEWS LAKE PLACID, N.Y. -- Students at Northwood School spent their Saturday afternoon raising money for a disease many people have never even heard of. Picture electrical cord. The rubber thats on the cord insulates those wires, well the myelin sheath Insulates all our nerves in our body, said Karen Fleming, Northwoods school nurse. People with a damaged myelin may develop multiple sclerosis or other myelin diseases. The students raised money for disease research, and held a tennis tournament, concert and three-mile walk. We get really into activities like this, and really do our part in charity work and hosting projects like this, said Emily Simmons, Student Council President. Students raise money for myelin disease research High schoolers in Lake Placid spent their weekend raising money for a good cause. The students were out in the community to spread the word about a little-known type of disease. Our Katie Morse has the story. ...

Zymenex sells clinical candidate Metazym to Shire

noemail@myelin.org — Thu, 08 May 2008 21:00:00 GMT

PRESS RELEASE April 24th, 2008 Zymenex sells clinical candidate Metazym to Shire for 135 MUSD Zymenex has – with the financial support of BankInvest Biomedical Venture and Sunstone Capital – achieved successful early clinical development of a therapeutic candidate Metazym against the rare, lethal and genetically caused, disease MLD, which most often affects children at a very young age. This has now resulted in a sale of the therapeutic project to the global specialty biopharmaceutical company Shire plc. Shire plc, which is quoted on the London Stock Exchange and Nasdaq, is one of the world’s largest specialty biopharmaceutical companies. Shire expects - after the acquisition of the Metazym project – to continue development and to seek to bring the product to market as quickly as possible. Shire, through its Human Genetic Therapies business, is a leading player in the development and commercialization of treatments against a number of lysosomal storage diseases, of...

Zymenex gets US Orphan Approval

noemail@myelin.org — Fri, 18 Apr 2008 22:00:00 GMT

P R E S S R E L E A S E Hillerød, Denmark, April 15, 2008 Zymenex gets US Orphan Approval The FDA has granted Zymenex Orphan Designation for its enzyme Metazym, for the treatment of the rare, lysosomal disease Metachromatic Leukodystrophy (MLD). Orphan designation qualifies the sponsor of the product for tax credits and marketing exclusivity incentives of the Orphan Drug Act. Zymenex has previously received Orphan Designation in the EU. Zymenex has just recently also received US FDA approval of its Investigational New Drug (IND) application, for its enzyme Metazym. Based on the successfully completed EU Phase 1 trial results, the company can go directly into Phase 2 clinical trials in the US. The US Phase 2 clinical trial is being conducted by Dr. Maria Escolar at the Program for Neurodevelopmental Function in Rare Disorders, Center for the Study of Development and Learning, University of North Carolina (UNC), Chapel Hill, North Carolina, USA. Metazym is in Phase 2...

DEVELOPMENT OF NEWBORN SCREENING TEST FOR ADRENOLEUKODYSTROPHY

noemail@myelin.org — Fri, 07 Mar 2008 18:00:00 GMT

When the Myelin Project was founded by Augusto and Michaela Odone, the little was known about ALD. Now, twenty years later, we not only know a great deal about the disease, we have treatments that, however imperfect, offer hope of survival for boys who carry the ALD gene. As published in 2005, Lorenzo’s Oil significantly reduces the risk of childhood cerebral ALD in boys carrying the ALD gene. Studies are now underway to discover whether Lorenzo’s oil will delay the onset and progression of adrenomyeloneuropathy in men and women who carry the ALD gene. There is also hope for those boys who carry the gene and develop symptoms of childhood cerebral ALD. When bone marrow transplant was first tried, the results were often very disappointing. Today, though, with advances in matching donors and recipient, and better pre- and post-operative therapies, the success rate is very high. The good news is that these advances give us hope that the specter of childhood cerebral ALD will be...

New Developments Therapy for Lorenzos Oil Boys

noemail@myelin.org — Wed, 31 Oct 2007 20:00:00 GMT

Doctors have for the first time used gene therapy to treat two boys with the rare nervous disorder made famous through the film Lorenzos Oil. Treatment for adrenoleukodystrophy has mainly involved bone marrow transplant, but this can be problematic due to lack of donors and rejection by the body. French doctors have now managed to modify the boys own bone marrow. They unveiled their findings at a summit of the European Society of Gene and Cell Therapy in Rotterdam. Adrenoleukodystrophy (ALD) is a rare inherited disorder that leads to progressive brain damage, failure of the adrenal gland and eventually death. It occurs because a flawed gene on the childs X chromosome means his body cannot produce an enzyme needed to break down fatty acids which can accumulate in the brain. There is no cure. Lorenzos Oil, a mixture of oleic acid and euric acid, is only really effective before the onset of symptoms. A team led by Patrick Aubourg, a professor at the Saint Vincent de Paul Hospital in...

Early Detection Called Key to Effectiveness

noemail@myelin.org — Sat, 01 Jan 2005 21:00:00 GMT

By Carey Goldberg, Globe Staff | July 12, 2005 New research offers scientific vindication for the parents whose fight to save their ailing son inspired the 1992 movie Lorenzos Oil. It comes too late to help the real-life Lorenzo, who is nearly totally paralyzed, but suggests that the oil could help save future generations of boys from the same, fatal nerve disorder. The paper, published yesterday in the Archives of Neurology, found that the oil was often effective at fending off symptoms in young boys who had the genetic disease that has devastated Lorenzo Odone. Among the 89 boys who started taking the oil before symptoms appeared, only 11 percent went on to develop them, compared with the usual 35 percent. In a prototypical clash between activist parents and resistant doctors, the medical establishment has been extremely skeptical about the effectiveness of Lorenzos oil. Among those skeptics was Dr. Hugo W. Moser, a professor at Johns Hopkins University and the lead author of the...